Crystal forms of glucosamine derivative, and preparation method therefor and use thereof

Abstract

The present invention relates to crystalline forms I and II of the compound 2-N-4,6-di-O-tributyryl-D-glucosamine, preparation methods and uses thereof, wherein the crystalline forms I and II obtained from the present invention have high water solubility, crystalline stability and can be better applied in pharmacy.

1 . A crystalline form I of a compound shown in the following formula I, wherein the crystalline form has characteristic peaks at diffraction angles of 5.13°, 5.73°, 6.79°, 19.41°, 19.73°, 21.78°, and 23.28° in the X-ray powder diffraction pattern expressed in terms of the angle of diffraction angle 2θ obtained using Cu-Kα radiation, wherein each diffraction angle has an error range of 0.2°: 
       
         
           
           
               
               
           
         
       
     
     
         2 . The crystalline form I according to  claim 1 , wherein the characteristic peaks are at diffraction angle 2θ of 5.13°, 5.73°, 6.79°, 10.28°, 10.85°, 11.49°, 13.58°, 14.49°, 16.23°, 18.14°, 19.41°, 19.73°, 20.97°, 21.78°, 23.28° and 25.07°, wherein each diffraction angle has an error range of ±0.2°. 
     
     
         3 . The crystalline form I according to  claim 1 , wherein the characteristic peaks are at diffraction angle 2θ of 5.13°, 5.73°, 6.79°, 8.10°, 10.28°, 10.85°, 11.49°, 13.58°, 14.49°, 16.23°, 18.14°, 18.46°, 19.41°, 19.73°, 20.44°, 20.97°, 21.78°, 22.10°, 23.07°, 23.28°, 23.62°, 24.07°, 25.07°, 26.87°, 27.41°, 28.94°, and 39.95°, wherein each diffraction angle has an error range of ±0.2°. 
     
     
         4 . The crystalline form I according to any of  claims 1-3 , wherein the crystalline form I has an onset temperature of the melting point peak of 109.06° C. and exhibits a maximum endothermic peak at 113.563° C. in a differential scanning calorimetry. 
     
     
         5 . A crystalline form II of a compound shown in the following formula I, wherein the crystalline form II has characteristic peaks at diffraction angles of 3.60°, 4.56°, 5.48°, 6.16°, 9.04°, 10.96°, 20.38°, and 32.97° in the X-ray powder diffraction pattern expressed in terms of the angle of diffraction angle 2θ obtained using Cu-Kα radiation, wherein each diffraction angle has an error range of ±0.2°: 
       
         
           
           
               
               
           
         
       
     
     
         6 . The crystalline form II according to  claim 5 , wherein the crystalline form II has an onset temperature of the melting point peak of 82.72° C. and exhibits a maximum endothermic peak at 92.32° C. in a differential scanning calorimetry. 
     
     
         7 . A method for preparing the crystalline form I according to any of  claims 1-4 , wherein the method comprises the steps of:
 dissolving the compound shown in formula I in a solvent;   subsequently subjecting the formulated solution to a heating-cooling cycle; wherein the heating-cooling cycle is performed by:
 equilibrating at 25° C. for 5 minutes; 
 heating to 80° C. at a rate of 1° C./min and holding at 80° C. for 30 minutes; 
 and then cooling to −20° C. at a rate of 1° C./min and holding for 2 hours; 
   wherein the solvent is acetonitrile.   
     
     
         8 . A method for preparing the crystalline form I according to any of  claims 1-4 , wherein the method comprises the following steps of:
 dissolving the compound shown in formula I in a good solvent to obtain a nearly saturated solution; and   lowering the temperature of the solution as completely dissolved to 0° C., then heating the solution from 20° C. to 25° C., adding a crystal seed, stirring and then obtaining a solid crystal; or,   raising the temperature of the solution as completely dissolved to 30° C., then cooling the solution to 25° C., adding a crystal seed, stirring and then obtaining a solid crystal.   
     
     
         9 . A method for preparing the crystalline form II according to  claim 5 or 6 , wherein the method comprises the steps of:
 dissolving the compound shown in formula I in a good solvent to obtain a nearly saturated solution; and   adding a poor solvent to the nearly saturated solution at 2 to 4 folds the volume of the solution to obtain a suspension, and then stirring the suspension at room temperature overnight;   wherein the good solvent is methyl tert-butyl ether; and the poor solvent is heptane.   
     
     
         10 . A pharmaceutical composition comprising the crystalline form I according to any of  claims 1-4  or the crystalline form II according to any of  claims 5-6 , and a pharmaceutically acceptable carrier. 
     
     
         11 . Use of the crystalline form I according to any of  claims 1-4  or the crystalline form II according to any of  claims 5-6  or the pharmaceutical composition according to  claim 10  in the preparation of a medication for the prevention or treatment of a bone or joint disease. 
     
     
         12 . The use according to  claim 10 , wherein the bone or joint disease is osteoporosis, osteopenia and/or arthritis. 
     
     
         13 . The use according to  claim 11 , wherein the arthritis is osteoarthritis, inflammatory arthritis (including rheumatoid arthritis or psoriatic arthritis), traumatic arthritis, degenerative arthritis, or dysplastic arthritis.